{"id":"b8e67d06-8477-52fc-b9c7-7bc74e0d7198","stable_key":"fe6af7fc-7372-5c4f-9c2f-2bbf56695397:phosphorus-casr-antagonism","predicate":"noncompetitively_inhibits","statement":"Raising extracellular phosphate inhibited CaSR activity through noncompetitive antagonism in the experimental system.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d03d5341-48cf-5022-81d8-27c0276a1468","mechanism_event_label":"Phosphate can act on the calcium-sensing receptor itself, not only change how much calcium is present.","subject":{"id":"ee63fe8e-92f3-552f-8049-a5f1fa1e1523","slug":"phosphate-ion","display_name":"Inorganic phosphate (Pi; protonation depends on pH)","entity_type_key":"ion"},"object":{"id":"1c0d5c58-d358-5501-9bdf-8999bcf79fd4","slug":"casr","display_name":"Calcium-sensing receptor / CaSR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"d03d5341-48cf-5022-81d8-27c0276a1468","stable_key":"fe6af7fc-7372-5c4f-9c2f-2bbf56695397:phosphorus-casr-antagonism-event","event_type":"biochemical_relationship","label":"Phosphate can act on the calcium-sensing receptor itself, not only change how much calcium is present.","description":"Raising extracellular phosphate inhibited CaSR activity through noncompetitive antagonism in the experimental system.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"other_receptor_input","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ee63fe8e-92f3-552f-8049-a5f1fa1e1523","slug":"phosphate-ion","display_name":"Inorganic phosphate (Pi; protonation depends on pH)","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"1c0d5c58-d358-5501-9bdf-8999bcf79fd4","slug":"casr","display_name":"Calcium-sensing receptor / CaSR","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/phosphorus-research/31619668.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d\", \"start_char\": 0, \"end_char\": 1144, \"text_sha256\": \"e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Phosphorus research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"phosphorus","display_name":"Phosphorus","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human CaSR expression system","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Phosphate can act on the calcium-sensing receptor itself, not only change how much calcium is present.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. 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